Atrial fibrillation (“AF”) is the most prevalent arrhythmia in clinical practice and a major contributor to morbidity and mortality. While some suffering from atrial fibrillation may experience no symptoms, those who do have atrial fibrillation symptoms may experience palpitations, which are sensations of a racing, uncomfortable, irregular heartbeat or a flopping in the chest, decreased blood pressure, weakness, lightheadedness, confusion, shortness of breath or chest pain, some of which may be rehabilitating. A recent study estimated that the number of Americans afflicted by AF will increase from the current range of 2.2 to 5.6 million to more than 12 million by 2050. This increase will be driven significantly by demographics, since AF affects nearly 4% of the U.S. population over 60 years of age. The enormity of the clinical problem is magnified by well-described sequelae: thromboembolic stroke, congestive heart failure (CHF), increased mortality and cognitive dysfunction. According to a recent report by the AF Stat™ working group, AF costs Medicare more than $15.7 billion annually due to costly complications. As the population continues to age, partially because of better therapies for atherosclerosis and heart failure, and becomes increasingly overweight, AF will become more prevalent, and its effect on morbidity and mortality will become even more important.
Although several milestones in the clinical management of AF have been met and many therapy options exist for AF, none fully meets the need of the large and growing patient base. Rhythm and rate control drugs represent typical first-line therapy but these are ineffective in significant numbers of patients. In addition, antiarrhythmic drugs in particular often have serious side effects. Anticoagulant drugs, administered to reduce the elevated risk of stroke, also have significant side effects, lack of efficacy in some patients, and compliance problems.
Conventional non-pharmacologic treatments of AF, such as external cardioversion, require costly patient hospitalization and anesthesia, and are frequently ineffective in that the arrhythmia concerned may recur within 12 months. Surgical ablation, whether performed on an open-chest or minimally-invasive basis, along with other surgical procedures such as excision of the left atrial appendage, carry their own risks and meet the needs of only a limited patient population. Newer left atrial appendage closure devices, approved for use in specified patients to reduce the potential generation of emboli, do not address the underlying condition and only address a portion of the patient population.
There have been many advances in catheter ablation techniques and these have brought significant advantages to the field. However, catheter ablations are still tedious procedures; and involve significant risks, which include cardiac perforation, esophageal injury, embolism, phrenic nerve injury, and pulmonary vein stenosis. In addition, recurrence 12 months after catheter ablation is reported in 5 to 10% of cases and has recently been reported in a range of 15% to 25% in different patient groups when follow-up is extended to around five years.
Implantable devices have been developed solely for AF therapy, and have generally fallen into five groups: atrial defibrillators, atrial burst stimulators, parasympathetic nerve stimulators, ventricular rate stabilization pacemakers and drug dispensers. The use of implantable atrial cardioverters (IACs) has previously been tried in patients with recurrent persistent AF. Although initial clinical trials of such early IAC devices indicated that they had high specificity and sensitivity to AF and delivered safe and effective shocks, they did not gain patient acceptance. This was primarily due to the fact that, given the technology employed at the time, the energy level needed to achieve cardioversion (˜3.0 J) greatly exceeded the pain threshold, causing great discomfort in patients who then opted to forego continued therapy.
For example, a first generation IAC, developed by InControl, was trialed in patients in the early 1990s. It was shown to provide prompt and safe restoration of sinus rhythm in patients with recurrent tachyarrhythmias. But it was not introduced to the market; primarily because patients could not tolerate the discomfort caused by the shocks which required approximately 3 Joules using conventional biphasic truncated exponential (BTE) shock therapy. Prior attempts to reduce the shock energy and voltage by providing pulsed waveforms, including ascending or other modified waveforms resulted in modest improvements, but these concepts were difficult to implement economically or physically in implantable devices.